Osteoclasts are large, multinucleated, bone-absorbing cells and play a crucial role in osteolytic bone diseases such as osteopetrosis and rheumatoid arthritis. Therefore, controlling osteoclast differentiation and activation has been considered a promising strategy to prevent and treat osteolytic diseases. In this study, we demonstrate, using the mouse monocyte-derived macrophage-like cell line RAW 264, that extract from Nasturtium officinale or watercress, an herb of European origin, suppresses receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation in vitro. N. officinale extract decreased the emergence of tartrate-resistant acid phosphatase-positive differentiated multinuclear cells and inhibited their bone-absorbing activity. The extract decreased expression of genes associated with osteoclast differentiation and function. Induction of nuclear factor of activated T cells c1 (NFATc1), the master transcriptional regulator of osteoclastogenesis, was blunted by N. officinale extract. Activation of nuclear factor-κB and mitogen-activated protein kinases pathways, both of which are necessary for NFATc1 induction and osteoclast differentiation, was also suppressed by the extract. Among upstream kinases, activity of IκB-kinase β (IKKβ), but not that of TGFβ-activated kinase 1, was inhibited by N. officinale extract in vitro. Pharmacological inhibition of IKKβ by a specific inhibitor PS1145 in RAW 264 cells mostly recaptured the inhibitory action of N. officinale extract. These findings provide a novel pharmacological action of N. officinale and its potential usefulness for the prevention of osteoporosis.

破骨细胞是大的、多核的、吸收骨的细胞，在溶骨性骨病（如骨硬化症和类风湿性关节炎）中起着至关重要的作用。因此，控制破骨细胞分化和活化被认为是预防和治疗溶骨性疾病的一种有前景的策略。在这项研究中，我们使用小鼠单核细胞衍生的巨噬细胞样细胞系 RAW 264 证明，从旱金莲或西洋菜（一种欧洲起源的草药）中提取的物质在体外抑制核因子-κB 配体诱导的破骨细胞分化的受体激活剂. 药用烟草提取物减少了抗酒石酸酸性磷酸酶阳性分化多核细胞的出现并抑制了它们的骨吸收活性。该提取物降低了与破骨细胞分化和功能相关的基因的表达。活化T核因子的诱导细胞 c1 (NFATc1) 是破骨细胞生成的主要转录调节因子，被 N. officinale 提取物钝化。提取物也抑制了核因子-κB 和丝裂原活化蛋白激酶途径的激活，这两者都是 NFATc1 诱导和破骨细胞分化所必需的。在上游激酶中，IκB 激酶 β (IKKβ) 的活性，而不是 TGFβ 活化激酶 1 的活性，在体外被 N. officinale 提取物抑制。在 RAW 264 细胞中，特异性抑制剂 PS1145 对 IKKβ 的药理学抑制主要恢复了药用植物提取物的抑制作用。这些发现提供了一种新的药理学作用 N. officinale 及其预防骨质疏松症的潜在用途。